Fig. 1 –

GPC3 cleavage as a potential target to reduce tumor growth. (A) Background (B) and tumor (T) from HB specimens shows increased GPC3 expression in tumor with areas of localization of presumed full-length (70 kDa) GPC3 (white arrow) and areas with N-terminus (40 kDa) staining only (yellow arrow) (40X objective, scale bar 50um). Five patient samples were evaluated with representative images shown. (B) Western blot of normal liver (N), human background (B) and tumor (T) samples from three HB patients (17, 18, 21 B/T), and one HCC patient (20 B/T), showing elevated GPC3 in tumor with more abundant GPC3 40 kDa cleaved product in HB compared to HCC (50 kDa band is also observed in tumor). Eight additional patient T/B samples were evaluated (data not shown). (C) Schematic demonstrating potential phenomena for an oncogenic form of proteins as a result of aberrant cleavage. Image created by BioRender.com. (D) Addition of cleaved GPC3 products (40 kDa and 30 kDa subunit peptides) and DNA construct transfection into SKHep1 cells results in increased proliferation with no change or reduced growth seen in cells treated with full-length (70 kDa) GPC3.